This research group continues to conduct clinically related basic research using human and experimental animal tissues to elucidate the underlying pathogenic mechanisms of ocular diseases, including cataracts, keratopathy, and retinopathy with the ultimate aim of improving means of diagnosing, treating, and preventing ocular disorders. The main emphasis has been on the possible means of preventing ocular complications of diabetes. The areas of focus include: 1) demonstrating the involvement of the polyol pathway in diabetic ocular complications using the galactose-fed rat model; 2) defining how damage to the lens epithelium relates to cataracts; 3) elucidating the relative roles of polyol and non-enzymatic glycosylation (glycation) in cataracts; 4) demonstrating diabetic-like corneal sensitivity loss in galactosemic rats and its amelioration with aldose reductase inhibitors; 5) applying computerized morphometric analysis to preparations of isolated, intact retinal vasculatures; 6) determining the efficacious timing for intervening in diabetic retinopathy; 7) investigating the roles of growth factors in diabetes-induced angiogenesis; 8) utilizing a model of retinopathy of prematurity to study angiogenesis; and 9) evaluating agents that induce and inhibit retinal and vitreal angiogenesis. Since neovascularization plays a central role in the blinding stages of diabetic retinopathy, yet is poorly understood, we are now expanding our investigations to include elucidation of the possible mechanisms involved in new vessel growth. We will be examining the potential for artificially modulating retinal and vitreal neovascularization using various agents, including growth factors, such as vascular endothelial growth factor (VEGF), and inhibitors of the same.